As described in U.S. Pat. No. 5,002,962, porphyrin related compounds accumulate at higher concentrations in tumor tissue as compared to normal tissue, and that irradiation of these compounds using light of the proper wavelength results in an energized form which, upon decay, results in cytotoxicity. It is believed that excitation of the porphyrin or related material results in the formation of singlet oxygen which is in fact the toxic agent. However, the compounds administered apparently do not degrade in this process.
Literature relating to the use of “hematoporphyrin derivative” (HPD) describes this process utilizing a preparation obtained when hematoporphyrin dichloride is treated using the procedure of Lipson, R. L., et al. J National Cancer Inst (1961) 26:1-8. More recently, it has been shown that if this hematoporphyrin derivative is treated at a suitable pH, aggregation occurs and the active material in the mixture can be prepared in crude form as a size segregated aggregate (see, for example, U.S. Pat. No. 4,649,151, incorporated herein by reference). This preparation is commercially available under the trademark Photofrin.
The preparation marketed as the Photofrin composition is a mixture. The mixture contains porphyrins joined by ether linkages (Dougherty, T. J., et al, Adv Exp Med Bio (1983) 160:3-13), and more recently, Kessel, D., et al Photochem Photobiol (1987) 46:463-568, has shown that ester linked porphyrins are contained in this mixture as well. Scourides, P. A., et al, Cancer Res (1987) 47:3439-3445 have synthesized an oligomeric mixture of ether linked porphyrins starting from hematoporphyrin dimethyl esters. The mixture was active in PDT, but was as complex a mixture as the Photofrin preparation. Dimers of hematoporphyrin joined by ester linkages have also been prepared by Pandey, R. K., et al, Cancer Res (in press) and the dimers prepared were shown to be absent from the mixture in the Photofrin composition as well as inactive in an in vitro assay.
Thus, it is known in the art that some elements of a mixture prepared when HPD is aggregated and segregated into higher molecular weight components are active in photodynamic therapy. Earlier, the present inventors prepared single compound compositions useful in PDT as disclosed in U.S. Pat. No. 5,002,962. The purified and defined compositions disclosed in U.S. Pat. No. 5,002,962 are useful in photodynamic therapy as are compounds and methods disclosed in U.S. Pat. Nos. 4,920,143 and 4,883,790.